Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239-3098, USA.
Dev Neurosci. 2011;33(3-4):251-60. doi: 10.1159/000327242. Epub 2011 Aug 25.
Progress in the development of rat models of human periventricular white matter injury (WMI) has been hampered by uncertainty about the developmental window in different rodent strains that coincides with cerebral white matter development in human premature infants. To define strain-specific differences in rat cerebral white matter maturation, we analyzed oligodendrocyte (OL) lineage maturation between postnatal days (P)2 and P14 in three widely studied strains of rat: Sprague-Dawley, Long-Evans and Wistar (W). We previously reported that late OL progenitors (preOL) are the major vulnerable cell type in human periventricular WMI. Strain-specific differences in preOL maturation were found at P2, such that the W rat had the highest percentage and density of preOL relative to the other strains. Overall, at P2, the state of OL maturation was similar to preterm human cerebral white matter. However, by P5, all three strains displayed a similar magnitude and extent of OL maturation that persisted with progressive myelination between P7 and P14. PreOL were the predominant OL lineage stage present in the cerebral cortex through P14, and thus OL lineage maturation occurred latter than in white matter. The hippocampus also displayed a later onset of preOL maturation in all three strains, such that OL lineage maturation and early myelination was not observed to occur until about P14. This timing of preOL maturation in rat cortical gray matter coincided with a similar timing in human cerebral cortex, where preOL also predominated until at least 8 months after full-term birth. These studies support that strain-specific differences in OL lineage immaturity were present in the early perinatal period at about P2, and they define a narrow window of preterm equivalence with human that diminishes by P5. Later developmental onset of preOL maturation in both cerebral cortex and hippocampus coincides with an extended window of potential vulnerability of the OL lineage to hypoxia-ischemia in these gray matter regions.
大鼠脑白质损伤（WMI）模型的发展一直受到阻碍，因为人们不确定不同品系大鼠的发育窗口与人类早产儿脑白质发育相吻合。为了确定大鼠脑白质成熟的品系特异性差异，我们分析了三种广泛研究的大鼠品系（Sprague-Dawley、Long-Evans 和 Wistar（W））在出生后第 2 天至第 14 天之间的少突胶质细胞（OL）谱系成熟情况。我们之前报道过，晚期 OL 前体细胞（preOL）是人类脑室周围 WMI 的主要易损细胞类型。在 P2 时，发现 preOL 成熟存在品系特异性差异，即 W 大鼠的 preOL 比例和密度相对于其他品系最高。总体而言，在 P2 时，OL 成熟状态与早产儿人类脑白质相似。然而，到 P5 时，所有三种品系的 OL 成熟程度相似，并且在 P7 至 P14 之间随着髓鞘形成而持续增加。在 P14 之前，preOL 是大脑皮层中存在的主要 OL 谱系阶段，因此 OL 谱系成熟发生在白质之后。海马体在所有三种品系中也显示出 preOL 成熟的较晚起始，因此直到 P14 左右才观察到 OL 谱系成熟和早期髓鞘形成。在大鼠皮质灰质中 preOL 成熟的这种时间与人类大脑皮质中类似的时间相吻合，在人类大脑皮质中，preOL 也一直占主导地位，直到足月出生后至少 8 个月。这些研究支持在大约 P2 的早期围产期存在 OL 谱系不成熟的品系特异性差异，并定义了与人类相似的早产儿等效性的狭窄窗口，该窗口在 P5 时缩小。皮质灰质中 preOL 成熟的后期发育开始与 OL 谱系对这些灰质区域缺氧缺血的潜在易损性的延长窗口相吻合。
